1. Field of the Invention
The invention relates to a compound and method for producing the same, and more particularly to a cefdinir acid double salt, a preparation method, and use thereof.
2. Description of the Related Art
Cefdinir was first synthesized by Fujisawa Company, Japan, in 1988 by modifying the structure of cefixime. It is the third generation of oral cephalosporin. The vinyl group linked to a mother ring carbon of cephalosporin improves the oral absorption rate thereof. The hydroxyl amino group and ammonia thiophene group at the side chain not only enhance the antibacterial activity against gram-negative bacteria and the stability of β-lactamase, but also improve the antibacterial activity against gram-positive bacteria, particularly against Staphylococcus aureus. The cefdinir preparations were first approved for sale in Japan in December, 1991, with a brand name of Cefzon, and then were sold in USA in December, 1997, with a brand name of Omnicef, and in Korea in 1999. Tianjin Centralpharm Co., Ltd. and Tianjin Institute of Pharmaceutical Research have cooperatively developed the production and synthesis of cefdinir and the dosage form of capsules and granules are obtained. The capsules have a brand name of Cefdinir Capsules, approved for sale in 2001 in China.
With a broad antimicrobial spectrum, high activity, good drug resistance, cefdinir is very excellent in the third generation of cephalosporin. However, it has obvious disadvantages such as low solubility and low bioavailability. Study shows that capsule cefdinir has a bioavailability of 16-20%, and for a liquid suspension, the bioavailability is merely 25%. Low bioavailability wastes drug resources, and the antibiotic residues easily cause side effect, e.g., intestinal flora disturbance and diarrhea. Furthermore, cefdinir is insoluble in water, and thus it cannot be prepared into an injection directly.
To solve the above disadvantages, a large number of researches have been conducted. Since the chemical structure of cefdinir includes carboxylic acids and amino group, a basic salt or acid salt thereof has been disclosed.
Chinese Pat. CN 1,415,615 discloses sodium cefdinir and a preparation method thereof. Chinese Pat. CN 1,251,590 discloses a salt synthesized by cefdinir and dicyclohexylamine. Chinese Pat. CN 1,512,996 discloses sulfate or mesylate cefdinir. U.S. Pat. No. 4,559,334 discloses the following cefdinir salt: sodium, potassium, calcium, magnesium, ammonium, organic ammonium, hydrochloric acid, sulfuric acid, bromated, phosphoric acid, formic acid, acetic acid, trifluoroacetic acid, maleic acid, tartaric acid, methanesulfonic acid, benzoic acid, arginine, aspartic acid, glutamic acid. KR20070088757 discloses a method for producing cesium cefdinir to purify cefdinir. DE60311869 discloses a method for producing phosphate cefdinir to purify cefdinir.
Cefdinir basic salts have poor stability.
The cefdinir salts recited in the above patents mainly target the purification of cefdinir. Prior to this disclosure, no cefdinir acid double salts or the benefits thereof have been reported.